Large-scale chromatin structure is the higher-order folding of chromatin on the scale of several hundred kilobases. Little is known about this folding, but the structures must influence transcription, replication and repair of DNA. To learn more about these structures, we have examined transcriptionally active domains of 400 - 2000 kb by light microscopy. We find that several different domains exhibit similar structures in light microscope images, namely a series of adjacent puncta or "beads" approximately 0.5 microns in diameter. When these same domains are transcriptionally inactive, only one punctum or "bead" is detected. Thus transcription induces a decondensation from single beaded to multi-beaded structures. These observations impose constraints on the higher order folding of chromatin. Present work focuses on identifying molecules associated with these structures, and observing the structures by higher resolution imaging.